Initial Workup of Thrombocytosis
The initial step in the workup of a patient with thrombocytosis should be to distinguish between primary (clonal) and secondary (reactive) causes through a complete blood count with peripheral smear review, testing for JAK2 mutation, and screening for underlying inflammatory conditions, infections, iron deficiency, and malignancies. 1
Diagnostic Algorithm for Thrombocytosis
Step 1: Define the Degree of Thrombocytosis
- Mild: 450,000-700,000/μL
- Moderate: 700,000-900,000/μL
- Severe: 900,000-1,000/μL
- Extreme: >1,000/μL 2
Step 2: Initial Laboratory Evaluation
- Complete blood count with differential
- Peripheral blood smear examination
- Comprehensive metabolic panel
- Inflammatory markers (ESR, CRP)
- Iron studies (ferritin, iron, TIBC)
- Testing for JAK2 V617F mutation 1, 3
- Screening for HCV and HIV 4
Step 3: Evaluate for Secondary Causes
Secondary causes account for 83.1% of thrombocytosis cases 5, including:
- Tissue injury (32.2%)
- Infection (17.1%)
- Chronic inflammatory disorders (11.7%)
- Iron deficiency anemia (11.1%) 5
- Recent surgery
- Malignancy
- Post-splenectomy 6
Step 4: Consider Primary Causes
If secondary causes are excluded, evaluate for myeloproliferative neoplasms (MPNs):
- Essential thrombocythemia
- Polycythemia vera
- Primary myelofibrosis
- Chronic myeloid leukemia 7
Key Diagnostic Tests for Primary Thrombocytosis
Molecular Testing:
Bone Marrow Examination:
- Indicated when primary thrombocytosis is suspected
- Not necessary for typical reactive thrombocytosis 1
- Critical for diagnosing MPNs and evaluating bone marrow morphology
Risk Stratification
Once the cause is determined, risk stratification is essential:
High-Risk Features:
- Age >60 years
- History of thrombosis
- JAK2 mutation positive
- Cardiovascular risk factors
- Platelet count >1,500 × 10^9/L 1
Low-Risk Features:
- Age ≤60 years
- No history of thrombosis
- No JAK2 mutation
- No cardiovascular risk factors 1
Common Pitfalls to Avoid
Premature Diagnosis: Avoid diagnosing primary thrombocytosis without excluding secondary causes, which are much more common.
Overlooking Iron Deficiency: Iron deficiency is a frequent cause of thrombocytosis and should be evaluated early in the workup 2, 3.
Missing Occult Malignancy: Thrombocytosis may be the presenting sign of solid tumors; appropriate age-appropriate cancer screening should be considered 3.
Unnecessary Bone Marrow Examination: Not required in cases of obvious reactive thrombocytosis, especially in children where primary thrombocytosis is extremely rare 2.
Inadequate Follow-up: If initial workup suggests reactive thrombocytosis but platelets remain elevated after addressing the underlying cause, reevaluation for primary causes is warranted.
By following this systematic approach, clinicians can efficiently determine the cause of thrombocytosis and develop an appropriate management plan based on whether the condition is primary or secondary, focusing on preventing complications such as thrombosis or hemorrhage that affect morbidity and mortality.